Efficient expansion of rare human circulating hematopoietic stem/progenitor cells in steadystate blood using a polypeptide-forming 3D culture
Received date: 13 Sep 2021
Accepted date: 14 Nov 2021
Published date: 15 Nov 2022
Copyright
Although widely applied in treating hematopoietic malignancies, transplantation of hematopoietic stem/progenitor cells (HSPCs) is impeded by HSPC shortage. Whether circulating HSPCs (cHSPCs) in steady-state blood could be used as an alternative source remains largely elusive. Here we develop a three-dimensional culture system (3DCS) including arginine, glycine, aspartate, and a series of factors. Fourteen-day culture of peripheral blood mononuclear cells (PBMNCs) in 3DCS led to 125- and 70-fold increase of the frequency and number of CD34+ cells. Further, 3DCS-expanded cHSPCs exhibited the similar reconstitution rate compared to CD34+ HSPCs in bone marrow. Mechanistically, 3DCS fabricated an immunomodulatory niche, secreting cytokines as TNF to support cHSPC survival and proliferation. Finally, 3DCS could also promote the expansion of cHSPCs in patients who failed in HSPC mobilization. Our 3DCS successfully expands rare cHSPCs, providing an alternative source for the HSPC therapy, particularly for the patients/donors who have failed in HSPC mobilization.
Yulin Xu , Xiangjun Zeng , Mingming Zhang , Binsheng Wang , Xin Guo , Wei Shan , Shuyang Cai , Qian Luo , Honghu Li , Xia Li , Xue Li , Hao Zhang , Limengmeng Wang , Yu Lin , Lizhen Liu , Yanwei Li , Meng Zhang , Xiaohong Yu , Pengxu Qian , He Huang . Efficient expansion of rare human circulating hematopoietic stem/progenitor cells in steadystate blood using a polypeptide-forming 3D culture[J]. Protein & Cell, 2022 , 13(11) : 808 -824 . DOI: 10.1007/s13238-021-00900-4
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